Wogonin induces retinal neuron-like differentiation of bone marrow stem cells by inhibiting Notch-1 signaling.
Wogonin induces retinal neuron-like differentiation of bone marrow stem cells by inhibiting Notch-1 signaling.
复制标题
汉黄芩素通过抑制Notch-1信号诱导骨髓干细胞的视网膜神经元样分化
DOI：
10.18632/oncotarget.16085
复制
发表时间：
2017-04-25
期刊：
影响因子：
--
通讯作者：
Xu G
中科院分区：
文献类型：
--
作者：
Shu Q;Zhuang H;Fan J;Wang X;Xu G
年龄相关性黄斑变性和色素性视网膜炎是老年人不可逆性视力丧失的主要原因，尽管人们持续努力，但目前的治疗方法在很大程度上是无效的。汉黄芩素是一种具有多种有益特性的生物活性植物黄酮类化合物，包括神经保护作用。我们研究了汉黄芩素促进骨髓干细胞（BMSCs）向视网膜神经元样分化的能力，并评估了Notch - 1信号通路在这一过程中的作用。培养的小鼠BMSCs在有或无汉黄芩素存在的情况下，不进行处理或暴露于神经营养因子，采用蛋白质印迹法、逆转录聚合酶链反应和免疫荧光法来鉴定干细胞特性和神经视网膜分化的分子标志物的变化。还通过蛋白质印迹法检测了作为神经发生主要负调控因子的Notch - 1信号通路中的蛋白质。我们发现，在汉黄芩素处理的BMSCs中，干细胞标志物的表达降低，而成熟视网膜神经元、双极细胞和光感受器的标志物增加。汉黄芩素还剂量依赖性地降低了Notch - 1信号蛋白的表达。此外，阻断Notch - 1既模拟又增强了汉黄芩素促进BMSCs分化为视网膜神经元样细胞的作用。因此，汉黄芩素似乎通过拮抗Notch - 1信号对神经发生的抑制作用来促进BMSCs向视网膜神经元样分化，并且可能在视网膜退行性疾病的治疗中有用。
Age-related macular degeneration and retinitis pigmentosa are major causes of irreversible vision loss in the elderly and, despite sustained efforts, current treatments are largely ineffective. Wogonin is a bioactive plant flavonoid possessing a range of beneficial properties, including neuroprotective effects. We investigated the ability of wogonin to promote retinal neuron-like differentiation of bone marrow stem cells (BMSCs) and assessed the involvement of Notch-1 signaling in this process. Cultured mouse BMSCs were left untreated or exposed to neurotrophic factors in the presence or absence of wogonin, and western blotting, RT-PCR and immunofluorescence were used to identify changes in molecular markers of stemness and neuroretinal differentiation. Proteins in the Notch-1 signaling pathway, a main negative regulator of neurogenesis, were also examined by western blotting. We found that expression of stem cell markers was reduced, while markers of mature retinal neurons, bipolar cells and photoreceptors were increased in wogonin-treated BMSCs. Wogonin also dose-dependently decreased expression of Notch-1 signaling proteins. Moreover, blockade of Notch-1 both mimicked and enhanced the effect of wogonin to facilitate BMSC differentiation into retinal neuron-like cells. Wogonin thus appears to promote retinal neuron-like differentiation of BMSCs by antagonizing the inhibitory actions of Notch-1 signaling on neurogenesis and may be useful in the treatment of retinal degenerative diseases.